| 1. |
- Senges, Christoph H.R., et al.
(author)
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Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation
- 2021
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In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 65:1
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Journal article (peer-reviewed)abstract
- This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. Comparison of proteomic responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology.
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| 2. |
- Abdallah, J., et al.
(author)
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Mechanical construction and installation of the ATLAS tile calorimeter
- 2013
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In: Journal of Instrumentation. - 1748-0221. ; 8, s. T11001-
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Journal article (peer-reviewed)abstract
- This paper summarises the mechanical construction and installation of the Tile Calorimeter for the ATLAS experiment at the Large Hadron Collider in CERN, Switzerland. The Tile Calorimeter is a sampling calorimeter using scintillator as the sensitive detector and steel as the absorber and covers the central region of the ATLAS experiment up to pseudorapidities +/- 1.7. The mechanical construction of the Tile Calorimeter occurred over a period of about 10 years beginning in 1995 with the completion of the Technical Design Report and ending in 2006 with the installation of the final module in the ATLAS cavern. During this period approximately 2600 metric tons of steel were transformed into a laminated structure to form the absorber of the sampling calorimeter. Following instrumentation and testing, which is described elsewhere, the modules were installed in the ATLAS cavern with a remarkable accuracy for a structure of this size and weight.
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| 3. |
- Brunel, Fabrice, et al.
(author)
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Structure and Yielding of Colloidal Silica Gels Varying the Range of Interparticle Interactions
- 2016
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 120:25, s. 5777-5785
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Journal article (peer-reviewed)abstract
- The relationship between interaction range, structure, fluid-gel transition, and viscoelastic properties of silica dispersions at intermediate volume fraction, φv ≈ 0.1 and in alkaline conditions, pH = 9 was investigated. For this purpose, rheological, physicochemical, and structural (synchrotron-SAXS) analyses were combined. The range of interaction and the aggregation state of the dispersions were tuned by adding either divalent counterions (Ca2+) or polycounterions (PDDA). With increasing calcium chloride concentration, a progressive aggregation was observed which precludes a fluid-gel transition at above 75 mM of calcium chloride. In this case, the aggregation mechanism is driven by short-range ion-ion correlations. Upon addition of PDDA, a fluid-gel transition, at a much lower concentration, followed by a reentrant gel-fluid transition was observed. The gel formation with PDDA was induced by charge neutralization and longer range polymer bridging interactions. The refluidification at high PDDA concentrations was explained by the overcompensation of the charge of the silica particles and by the steric repulsions induced by the polycation chains. Rheological measurements on the so-obtained gels reveal broad yielding transition with two steps when the size of the silica particle clusters exceeds ≈0.5 μm.
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| 4. |
- Hasseln, Herman, et al.
(author)
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The future design scenario and the SEA initiative
- 2004
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In: IFAC Symposium on Advances in Automotive Control.
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Conference paper (peer-reviewed)abstract
- The overall objective of the SEA Initiative is to develop a framework and aseamless process-flow for the design of complex embedded real-time systems inautomotive applications. Both framework and process -flow need to support the entireautomotive design chain from car manufacturers to subsystem providers, from IPproviders to semiconductor developers. These objectives address several key issues facedby the automotive industry, e.g. system complexity and efficiency:For the car manufacturer, where an increasing number of complex subsystems developedels ewhere have to be interfaced correctly and efficiently during system integration inpresence of increasing pressure for faster introduction of new models in the market place.For the subsystem suppliers, where the requirements on quality and costs become tighterwhile the features demanded become more complex, demanding designs withincreasingly larger software content and more performing hardware. For automotivesemiconductor and IP providers, who find it increasingly difficult to meet the reliabilityand performance requirements demanded by their customers while providing theirproducts so that they could be easily integrated and offer the performance required
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| 5. |
- Karam, Elias, et al.
(author)
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Outcomes of rescue procedures in the management of locally recurrent ampullary tumors : A Pancreas 2000/EPC study
- 2023
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In: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 173:5, s. 1254-1262
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Journal article (peer-reviewed)abstract
- Background: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. Methods: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. Results: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. Conclusion: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.
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